Sten Tibblin

Unilateral versus bilateral neck exploration for primary hyperparathyroidism: a prospective randomized controlled trial.

ObjectiveTo compare unilateral and bilateral neck exploration for primary hyperparathyroidism in a prospective randomized controlled trial. Summary Background DataBased on the assumption that unilateral neck exploration for a solitary parathyroid adenoma should reduce operating time and morbidity, a variety of minimally invasive procedures have challenged the idea that bilateral neck exploration is the gold standard for the surgical treatment of primary hyperparathyroidism. However, to date, no open prospective randomized trial has been published comparing unilateral and bilateral neck exploration. MethodsNinety-one patients with the preoperative diagnosis of primary hyperparathyroidism were randomized to unilateral or bilateral neck exploration. Preoperative scintigraphy and intraoperative parathyroid hormone measurement guided the unilateral exploration. Gross morphology and frozen section determined the extent of parathyroid tissue resection in the bilateral group. The primary end-point was the use of postoperative medication for hypocalcemic symptoms. ResultsEighty-eight patients (97%) were cured. Histology and cure rate did not differ between the two groups. Patients in the bilateral group consumed more oral calcium, had lower serum calcium values on postoperative days 1 to 4, and had a higher incidence of early severe symptomatic hypocalcemia compared with patients in the unilateral group. In addition, for patients undergoing surgery for a solitary parathyroid adenoma, unilateral exploration was associated with a shorter operative time. The cost for the two procedures did not differ. ConclusionsPatients undergoing a unilateral procedure had a lower incidence of biochemical and severe symptomatic hypocalcemia in the early postoperative period compared with patients undergoing bilateral exploration. Unilateral neck exploration with intraoperative parathyroid hormone assessment is a valid surgical strategy in patients with primary hyperparathyroidism with distinct advantages, especially for patients with solitary parathyroid adenoma.

Oxyphil tumors of the thyroid: follow-up of 42 surgical cases.

Histopathologic and clinical follow-up data on 42 patients observed 2-20 years after operations for oxyphil neoplasms of the thyroid are presented. In eight patients histologic signs of malignancy were found but only two patients showed a clinically malignant course with development of distant metastases. The results do not indicate that oxyphil thyroid neoplasms are especially prone to assume a malignant course with the mode of treatment applied. Our policy is to remove any differentiated epithelial thyroid neoplasm with at least lobectomy. Total thyroidectomy is reserved for cases with capsular penetration, blood vessel invasion and/or metastases.

Immunohistochemical evidence of peptide hormones in endocrine tumors of the rectum

Twenty‐five endocrine tumors of the rectum (rectal carcinoids) were examined immunohistochemically for various pancreatic and gut neurohormonal polypeptides. Twenty‐one of the tumors were found to contain cells displaying pancreatic polypeptide (PP), glucagon, somatostatin, insulin, substance P, enkephalin or β‐endorphin immunoreactivity. At least 11 of the tumors contained more than one peptide hormone. In some of the tumors PP cells made up the major cell population, in others the glucagon cells constituted the majority. Only four of the tumors contained 5‐hydroxytryptamine. Rectal endocrine tumors seem unique among gut endocrine tumors in that they may store immunoreactive enkephalin, β‐endorphin and even insulin. None of the patients displayed the carcinoid syndrome; symptoms were usually vague and uncharacteristic. In many cases the tumor was found at routine examination.

Persistent elevated serum levels of intact parathyroid hormone after operation for sporadic parathyroid adenoma: Evidence of detrimental effects of severe parathyroid disease*

BACKGROUND A significant number of patients with primary hyperparathyroidism (pHPT) who are surgically treated have increased serum levels of intact parathyroid hormone (PTH) during long-term follow-up despite normocalcemia. The cause and significance of this finding remain to be established. METHODS A total of 82 patients operated on for sporadic parathyroid adenoma were investigated before and at 8 weeks and 1 year after operation with serum levels of intact PTH, bone mineral content, and biochemical variables known to reflect PTH activity. RESULTS All patients had low or normal serum levels of calcium during follow-up. At 8 weeks after operation 20 (24%) patients had increased serum levels of PTH. These patients had severe parathyroid disease and low levels of 25(OH) vitamin D before operation. In contrast to patients with normal levels of PTH after operation, they did not have an elevated bone mineral content but had elevated levels of serum creatinin. At 1 year after operation 13 patients had elevated serum levels of PTH. Compared with patients with normal serum levels of PTH, they were older and had an increased frequency of cardiovascular disease and biochemical indications of compromised renal function. They did not have an elevated bone mineral content. CONCLUSIONS Persistently increased serum levels of PTH indicate harmful effects of pHPT even after surgical cure, especially in elderly patients with severe disease before operation. The results in this investigation therefore favor early treatment of pHPT.

Sestamibi versus thallium subtraction scintigraphy in parathyroid localization : a prospective comparative study in patients with predominantly mild primary hyperparathyroidism

BACKGROUND Technetium 99m sestamibi was recently introduced for the preoperative localization of abnormal parathyroid glands in patients with primary hyperparathyroidism with promising results. However, the sensitivity of sestamibi and thallium to detect abnormal parathyroid glands is partly dependent on the gland size. In this study we compared the sensitivity of sestamibi subtraction scintigraphy with thallium subtraction scintigraphy in patients with predominantly mild increase in serum calcium level. METHODS Thirty-nine patients with primary hyperparathyroidism were included. The mean (+/-SD) serum level of calcium was 2.75 +/- 0.17 mmol/L. In 28 (72%) of the patients the serum level of calcium was less than 2.85 mmol/L. These patients were classified as having mild abnormalities in serum calcium. All patients were investigated before operation with both sestamibi and thallium subtraction scintigraphy. RESULTS In two patients autonomous thyroid adenomas precluded subtraction scintigraphy. Sestamibi subtraction scintigraphy correctly localized 31 (86%) of 36 parathyroid adenomas compared with only 17 (47%) of 36 by thallium subtraction scintigraphy (p < 0.001). There was one false-positive result in the sestamibi group because of a thyroid adenoma, and two of the scans were negative. Both the sestamibi and the thallium subtraction scintigraphy localized one single enlarged gland in all three patients with multiple gland involvement. In no case was multiglandular disease predicted. CONCLUSIONS Sestamibi subtraction scintigraphy is superior to thallium subtraction scintigraphy and has a high sensitivity to localize a solitary parathyroid adenoma in patients with mild increase in serum calcium level. The sensitivity decreases in patients with multiglandular parathyroid disease and concomitant thyroid nodular abnormalities.

Fat staining in parathyroid disease—Diagnostic value and impact on surgical strategy: Clinicopathologic analysis of 191 cases

The study comprised 191 cases of surgically treated hyperparathyroidism, with all principal types of parathyroid disease represented. At least two complete glands stained with a modified isopropanol oil red O method for fat, in addition to sections stained with hematoxylin-eosin, were available in each case. On the basis of the morphologic evaluation and the clinical follow-up data, it is concluded that access to two complete glands and the use of fat staining allow highly reliable intraoperative distinction between adenoma and hyperplasia. Of 105 patients followed up for at least one year (mean, 20 months) in whom adenomas were diagnosed, a single possible error was identified. In each of 68 cases classified as hyperplasia on the basis of two abnormal glands, every additional complete gland available (total, 182 glands) was at least partially abnormal, with distinct signs of hyperactivity, irrespective of size. The rate of equivocal findings for cases in which two glands were available (probably adenoma but hyperplasia not excluded) was 8 per cent in 165 cases of primary hyperparathyroidism. These results justify limitation of surgery to one side of the neck in patients in whom adenoma is diagnosed on the basis of a complete, functionally normal (inactive) gland in addition to the presumed adenoma. Thus, the methods described provide a basis for optimal utilization of imaging techniques that allow preoperative localization of parathyroid adenomas.

Surgical strategy in hyperparathyroidism due to solitary adenoma.

Based on the postulate that parathyroid adenoma is practically always a solitary lesion, unilateral parathyroidectomy including the homolateral normal parathyroid was applied as a principle in the treatment of this form of primary hyperparathyroidism. The exploration was confined to the adenoma side if this was the first to be explored. Intraoperative oil-red-O staining of frozen sections was used to exclude the possibility of a multiglandular involvement. This principle was applied in a consecutive series of 102 patients operated for hyperparathyroidism from 1977 to 1981 and diagnosed as parathyroid adenoma. In 43 patients where the abnormal gland was found on the side explored first, unilateral parathyroidectomy was performed on that side, avoiding exploration of the contralateral side. In 45 patients where normal glands were found on the side first explored, unilateral parathyroidectomy was performed on the contralateral side. In 14 patients other types of operations were performed as the above-mentioned principle could not be achieved. At follow-up 1 to 5 years after surgery, no cases of hypocalcemia were recorded. The results of the different operations were compared as to early and late hypocalcemia. Early hypercalcemia was more pronounced after a bilateral exploration. Two of the patients who had an atypical operation had a permanent need for vitamin D in order to maintain an adequate serum calcium level. Surgical principles for various possible exploratory findings are outlined. These are based upon the idea of performing a unilateral parathyroidectomy whenever intraoperative oil-red-O staining excludes multiglandular involvement as a cause for the hyperparathyroidism.

Hyperparathyroidism in the elderly.

Primary hyperparathyroidism was studied in a well-defined geriatric population of 1129 individuals during a three-month interval. Primary hyperparathyroidism was diagnosed in 1.5%. The diagnosis was based on a morphologic and biochemic basis. From clinical material consisting of 400 patients treated surgically for primary hyperparathyroidism during a ten-year period, 158 patients (38%) above the age of 64 were studied. At the preoperative evaluation, neuromuscular symptoms were present in 80%, renal insufficiency and kidney stones in each 16%, constipation and/or anorexia in 38%. Ten per cent were considered asymptomatic. In 80% the primary hyperparathyroidism was caused by a solitary adenoma. Ninety-four per cent became normocalcemic following the operation. Consistent hypocalcemia requiring vitamin-D treatment occurred in 3%, and 2% had a persisting hypercalcemia or later recurrence. The therapeutic effect on the neuromuscular symptoms, constipation, anorexia, and renal stone formation was considered good or fair in most of the cases. Primary hyperparathyroidism in the elderly occurs with a high prevalence. It can be treated successfully by surgical therapy with a low cost of morbidity, mortality, and medical care.

Thyroid carcinoma in Malmö, 1960-1977. Epidemiologic, clinical, and prognostic findings in a defined urban population.

One hundred four cases of clinically significant thyroid carcinoma (TC) occurred in a demographically well defined area with, on an average, 243,000 inhabitants, during an 18‐year period, corresponding to a yearly incidence of 2.4 per 100,000. During the later years of the study there was an increase of the age‐standardized incidence of differentiated TC. The reason for this is suggested to be a greater health awareness, because only the number of tumors with less advanced growth increased. Sixty‐one patients had, as the only presenting sign, a solitary thyroid nodule, while 24 had obviously malignant disease. All cases were revised histologically. Sixty‐six patients were found to have papillary carcinoma, whereas 22 cases were diagnosed as follicular, 4 as medullary, and 12 as anaplastic. The prognosis, as estimated by the life‐table method, was worse for patients with anaplastic cancer followed by follicular, papillary, and medullary. Within the papillary group, patients with occult cancer, i.e., thyroid tumor not larger than 1.5 cm, and intrathyroidal cancer, i.e., thyroid tumor larger than 1.5 cm but not penetrating the thyroid capsule, had a cumulated survival rate not significantly different from the expected rate, and only 1 of the 46 patients belonging these two subgroups, died from TC.

Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease

Valdemarsson S, Lindergård B, Tibblin S, Bergenfelz A (Lund University Hospital, Sweden). Increased biochemical markers of bone formation and resorption in primary hyperparathyroidism with special reference to patients with mild disease. J Intern Med 1998; 243: 115–22.